U.S. Pat. No. 4,064,118 describes a composition useful as a blood substitute or a blood extender which comprises the water soluble product of covalently coupling haemoglobin with dextran having a molecular weight of from about 5,000 to about 2,000,000.
It has however been found that, as compared with haemoglobin, the products according to U.S. Pat. No. 4,064,118 tend to show a somewhat greater affinity for oxygen, but retain the essential oxygen transporting and releasing capability of haemoglobin.
U.S. Pat. No. 4,650,786 describes a modified dextran-haemoglobin complex having reduced oxygen affinity. This modified dextran-haemoglobin complex is prepared by first activating the dextran moeity, and then reacting the activated dextran with haemoglobin or a haemoglobin-inositol tetrakis phosphate dialdehyde (FPA) complex.
However, dextran-haemoglobin complexes and modified dextran-haemoglobin complexes suffer from the disadvantage that the viscosity of an aqueous solution increases on storage, e.g. for 12 days or more, to such an extent so as to render them unsuitable for administration.
We have now surprisingly found that the activated sites on the dextran moiety may be blocked, and the viscosity on storage improved, without affecting the oxygen transport properties of the haemoglobin complex.